M1 and M2 Macrophages: Oracles of Health and Disease

Crit Rev Immunol. 2012;32(6):463-88. doi: 10.1615/critrevimmunol.v32.i6.10.


The purpose of immunology is simple. Cure or prevent disease. M1/M2 is useful because it is simple. M1/M2 describes the two major and opposing activities of macrophages. M1 activity inhibits cell proliferation and causes tissue damage while M2 activity promotes cell proliferation and tissue repair. Remarkably, the molecules primarily responsible for these "Fight" (NO) or "Fix" (Ornithine) activities both arise from arginine, and via enzymatic pathways (iNOS and arginase) that down regulate each other. The names M1 and M2 were chosen because M1 and M2 macrophages promote Th1 and Th2 responses, respectively. Products of Th1 and Th2 responses (e.g., IFN-γ, IL-4) also down regulate M2 and M1activity, respectively. Thus, M1/M2 demonstrated the importance of Innate Immunity and how it is linked to Adaptive Immunity in a beautifully counterbalanced system. "Civilization" and increased longevity present new disease challenges such as cancer and atherosclerosis that do not display classical "foreign" antigens. And, these diseases are often associated with (or caused by) M1- or M2- type responses that were formerly useful for fighting infections, but now are inappropriate in our increasingly "germ-free" societies. In turn, there is considerable potential for modulating M1 or M2 Innate responses in modern diseases to achieve better health. Finally, since M1 and Th1 (or M2 and Th2) often work in concert to produce characteristic immune responses and disease pathologies, it is recommended that Immune Type 1 or 2 (IT1, IT2) would be a simpler and unifying terminology going forward.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Apoptosis
  • Arginine / analogs & derivatives
  • Arginine / metabolism*
  • Autoimmunity
  • Cell Differentiation
  • Cell Proliferation
  • Cytokines / immunology
  • Humans
  • Immunity, Innate
  • Macrophages / immunology*
  • Nitric Oxide / metabolism*
  • Ornithine / metabolism*
  • Th1-Th2 Balance
  • Wound Healing


  • Cytokines
  • Nitric Oxide
  • Arginine
  • Ornithine